Comparison of Phenolic Compounds and Evaluation of Antioxidant Properties of Porophyllum ruderale (Jacq.) Cass (Asteraceae) from Different Geographical Areas of Queretaro (Mexico).

Porophyllum ruderale (P. ruderale) is a well-known Mexican plant from the group of "Quelites", widely consumed plant species used for several food and medicinal purposes. As the production is very heterogeneous and the diverse agroclimatic conditions significantly impact the plant's phytochemical composition, this research aimed to compare the phenolic compound composition and the antioxidant capacity of the P. ruderale plant from three different collection sites (Queretaro, Landa de Matamoros, and Arroyo Seco) in the State of Queretaro (Mexico). Plants collected from Queretaro displayed the lowest total phenolic compounds, flavonoids, and condensed tannins, reflected in a lower antioxidant capacity (DPPH, FRAP, ABTS), compared to the other collection places. Flavones (epicatechin and epigallocatechin gallate) were the most abundant (36.1-195.2 µg equivalents/g) phenolics quantified by HPLC-DAD, while 31 compounds were identified by UHPLC-DAD-QToF/MS-ESI. Most compounds were linked to biological mechanisms related to the antioxidant properties of the leaves. A PCA analysis clustered Landa de Matamoros and Arroyo Seco into two groups based on flavones, hydroxybenzoic acids, the antioxidant capacity (ABTS and DPPH), and total phenolic compounds, the main contributors to its variation. The results indicated contrasting differences in the polyphenolic composition of collected P. ruderale in Queretaro, suggesting the need to standardize and select plants with favorable agroclimatic conditions to obtain desirable polyphenolic compositions while displaying potential health benefits.

Comparison of Phytochemical Composition and Untargeted Metabolomic Analysis of an Extract from Cnidoscolus aconitifolius (Mill.) I. I. Johnst and Porophyllum ruderale (Jacq.) Cass. and Biological Cytotoxic and Antiproliferative Activity In Vitro.

Cnidoscolus aconitifolius (CA) and Porophyllum ruderale (PR) are representative edible plants that are a traditional food source in Mexico. This research aimed to analyze the phytochemical composition and untargeted metabolomics analysis of CA and PR and evaluate their antiproliferative effect in vitro. The phytochemical composition (UPLC-DAD-QToF/MS-ESI) identified up to 38 polyphenols and selected organic acids that were clustered by the untargeted metabolomics in functional activities linked to indolizidines, pyridines, and organic acids. Compared with PR, CA displayed a higher reduction in the metabolic activity of human SW480 colon adenocarcinoma cells (LC50: 10.65 mg/mL), and both extracts increased the total apoptotic cells and arrested cell cycle at G0/G1 phase. PR increased mRNA Apc gene expression, whereas both extracts reduced mRNA Kras expression. Rutin/epigallocatechin gallate displayed the highest affinity to APC and K-RAS proteins in silico. Further research is needed to experiment on other cell lines. Results suggested that CA and PR are polyphenol-rich plant sources exhibiting antiproliferative effects in vitro.

Biogenic Silver Nanoparticles and Stressors Generate Synergistic Growth Inhibition in Candida Species through Cell Wall Damage, Osmotic Stress, and Oxidative Stress.

BACKGROUND: The need to combat and reduce the incidence, virulence, and drug resistance of species belonging to Candida genus, has led to the development of new strategies. Nanotechnology, through the implementation of nanomaterials, has emerged as an infallible tool to treat various diseases caused by pathogens, where its mechanisms of action prevent the development of undesirable pharmacological resistance. OBJECTIVE: The antifungal activity and adjuvant properties of biogenic silver nanoparticles in different Candida species (C. parapsilosis, C. glabrata, and C. albicans) are evaluated. METHODS: The biogenic metallic nanoparticles were developed by quercetin-mediated biological synthesis. The physicochemical properties were studied by light scattering, electrophoretic mobility, UV-vis and infrared spectroscopy, and transmission electron microscopy. The elucidation of mechanisms of antifungal action was carried out under stress conditions in Candida species at the cell wall and response to oxidative stress. RESULTS: Small silver nanoparticles (≈ 16.18 nm) with irregular morphology, and negative surface electrical charge (≈ -48.99 mV), were obtained through quercetin-mediated biosynthesis. Infrared spectra showed that the surface of silver nanoparticles is functionalized with the quercetin molecule. The antifungal activity of biogenic nanoparticles had efficacy in the following trend C. glabrata ≥ C. parapsilosis > C. albicans. Biogenic nanoparticles and stressors showed synergistic and potentiated antifungal effects through cell damage, osmotic stress, cell wall damage, and oxidative stress. CONCLUSIONS: Silver nanoparticles synthesized by quercetin-mediated biosynthesis could be implemented as a powerful adjuvant agent to enhance the inhibition effects of diverse compounds over different Candida species.

Quercetin and Its Fermented Extract as a Potential Inhibitor of Bisphenol A-Exposed HT-29 Colon Cancer Cells' Viability.

Bisphenol A (BPA) promotes colon cancer by altering the physiological functions of hormones. Quercetin (Q) can regulate signaling pathways through hormone receptors, inhibiting cancer cells. The antiproliferative effects of Q and its fermented extract (FEQ, obtained by Q gastrointestinal digestion and in vitro colonic fermentation) were analyzed in HT-29 cells exposed to BPA. Polyphenols were quantified in FEQ by HPLC and their antioxidant capacity by DPPH and ORAC. Q and 3,4-dihydroxyphenylacetic acid (DOPAC) were quantified in FEQ. Q and FEQ exhibited antioxidant capacity. Cell viability with Q+BPA and FEQ+BPA was 60% and 50%, respectively; less than 20% of dead cells were associated with the necrosis process (LDH). Treatments with Q and Q+BPA induced cell cycle arrest in the G0/G1 phase, and FEQ and FEQ+BPA in the S phase. Compared with other treatments, Q positively modulated ESR2 and GPR30 genes. Using a gene microarray of the p53 pathway, Q, Q+BPA, FEQ and FEQ+BPA positively modulated genes involved in apoptosis and cell cycle arrest; bisphenol inhibited the expression of pro-apoptotic and cell cycle repressor genes. In silico analyses demonstrated the binding affinity of Q > BPA > DOPAC molecules for ERα and ERß. Further studies are needed to understand the role of disruptors in colon cancer.

Fermentation Extract of Naringenin Increases the Expression of Estrogenic Receptor ß and Modulates Genes Related to the p53 Signalling Pathway, miR-200c and miR-141 in Human Colon Cancer Cells Exposed to BPA.

The estrogenic receptor beta (ERß) protects against carcinogenesis by stimulating apoptosis. Bisphenol A (BPA) is related to promoting cancer, and naringenin has chemoprotective activities both can bind to ERß. Naringenin in the colon is metabolized by the microbiota. Cancer involves genetic and epigenetic mechanisms, including miRNAs. The objective of the present study was to evaluate the co-exposure effect of colonic in vitro fermented extract of naringenin (FEN) and BPA, to elucidate molecular effects in HT-29 colon cancer cell line. For this, we quantified genes related to the p53 signaling pathway as well as ERß, miR-200c, and miR-141. As an important result, naringenin (IC50 250 µM) and FEN (IC50 37%) promoted intrinsic pathways of apoptosis through phosphatase and tensin homolog (PTEN) (+2.70, +1.72-fold, respectively) and CASP9 (+3.99, +2.03-fold, respectively) expression. BPA decreased the expression of PTEN (-3.46-fold) gene regulated by miR-200. We suggest that once co-exposed, cells undergo a greater stress forcing them to mediate other extrinsic apoptosis mechanisms associated with death domain FASL. In turn, these findings are related to the increase of ERß (5.3-fold with naringenin and 13.67-fold with FEN) gene expression, important in the inhibition of carcinogenic development.

Chitosan-G-Glycidyl Methacrylate/Au Nanocomposites Promote Accelerated Skin Wound Healing.

Herein, we report the synthesis of Au nanoparticles (AuNPs) in chitosan (CTS) solution by chemically reducing HAuCl4. CTS was further functionalized with glycidyl methacrylate (chitosan-g-glycidyl methacrylate/AuNP, CTS-g-GMA/AuNP) to improve the mechanical properties for cellular regeneration requirements of CTS-g-GMA/AuNP. Our nanocomposites promote excellent cellular viability and have a positive effect on cytokine regulation in the inflammatory and anti-inflammatory response of skin cells. After 40 days of nanocomposite exposure to a skin wound, we showed that our films have a greater skin wound healing capacity than a commercial film (TheraForm®), and the presence of the collagen allows better cosmetic ave aspects in skin regeneration in comparison with a nanocomposite with an absence of this protein. Electrical percolation phenomena in such nanocomposites were used as guiding tools for the best nanocomposite performance. Our results suggest that chitosan-based Au nanocomposites show great potential for skin wound repair.

Garambullo (Myrtillocactus geometrizans): effect of in vitro gastrointestinal digestion on the bioaccessibility and antioxidant capacity of phytochemicals.

Garambullo (Myrtillocactus geometrizans), endemic fruit from Mexico, contains several bioactive compounds (phenolic compounds, betalains, antioxidant fiber), highlighting it as a good functional food. In this research, the impact of the in vitro gastrointestinal digestion on phytochemical bioaccessibility from garambullo and its antioxidant capacity are studied. The fruit contained previously unidentified phytochemicals in the polar and non-polar extracts (acetone and hexane). The bioaccessibility decreased in the mouth and stomach for flavanones (up to 11.9 and 8.9%, respectively), isoflavones (up to 20.0 and 9.2%, respectively), flavonols (up to 15.2 and 15.7%, respectively), hydroxycinnamic acids (up to 21.7 and 13.1%, respectively), and betalains (up to 10.5 and 4.2%, respectively); hydroxybenzoic acids were increased (up to 752.8 and 552.6%, respectively), while tocopherols increased in the mouth (127.7%) and decreased in the stomach (up to 90.3%). In the intestinal phase, the digestible fraction showed low phytochemicals bioaccessibility, and some compounds were recovered in the non-digestible fraction. The antioxidant capacity decreased in different compartments of the gastrointestinal tract, being higher in the mouth (872.9, 883.6, 385.2, and 631.2 µmol TE per g dw by ABTS, DPPH, ORAC, and FRAP, respectively) and stomach (836.2, 942.1, 289.0, and 494.9 µmol TE per g dw ABTS, DPPH, ORAC, and FRAP, respectively). The results indicate that digestion positively or negatively affects compounds' bioaccessibility depending on their structural family, and the antioxidant capacity decreases but remains higher than other functional foods.

Low Serum B12 Concentrations Are Associated with Low B12 Dietary Intake But Not with Helicobacter pylori Infection or Abnormal Gastric Function in Rural Mexican Women.

BACKGROUND: Gastric function, Helicobacter pylori infection, and vitamin B12 (B12) dietary intake were assessed as predictors of serum B12. METHODS: H. pylori antibodies, gastric function, B12 dietary intake, and biochemical/hematological parameters were measured in 191 adult women from two rural communities in Querétaro, Mexico. RESULTS: The overall mean serum B12 concentration was 211 ± 117 pmol/L. The prevalences of low (≤ 148 pmol/L), marginal (148 to 221 pmol/L), and adequate (> 221 pmol/L) serum B12 were 28.4%, 31.1%, and 40.5%, respectively. Seventy-one percent of women tested positive for H. pylori antibodies. The prevalence of gastric function categories did not differ by serum B12 categories. The odds ratio for having low serum B12 was 2.7 (p = 0.01) for women with an intake below the estimated average requirement, 3.6 (p = 0.01) for those in the lowest tertile of total B12 intake, and 3.0 (p = 0.02) for those in the lowest tertile of B12 intake from animal source foods. Age and B12 intake were predictors of serum B12 concentrations [serum B12 (pmol/L) = 90.060 + 5.208 (B12 intake, µg/day) + 2.989 (age, years). CONCLUSIONS: Low serum B12 concentrations were associated with low B12 dietary intake but not with H. pylori infection or abnormal gastric function in rural Mexican women.

Development of genistein-PEGylated silica hybrid nanomaterials with enhanced antioxidant and antiproliferative properties on HT29 human colon cancer cells.

The anticancer use of genistein (Gen) has been severely limited due to its low water solubility, low bioavailability, and instability under experimental conditions. To overcome these limitations, we propose a formulation of a hybrid nanomaterial (HNM) based upon the incorporation of Gen into PEGylated silica nanoparticles (PEG-SiNPs) (Gen-PEG-SiHNM), where their physicochemical and biological effects on HT29 cells were evaluated. Genistein-loaded PEGylated silica hybrid nanomaterials were obtained by a simple end effective aqueous dispersion method. Physicochemical properties were determined by its mean particle size, surface charge, amount of cargo, spectroscopic properties, release profiles and aqueous solubility. In vitro biological performance was carried out by evaluating its antioxidant capacity and elucidating its antiproliferative mechanistic. Results showed that small (ca. 33 nm) and spherical particles were obtained with positive surface charge (+9.54 mV). Infrared analyses determined that encapsulation of genistein was successfully achieved with an efficiency of 51%; it was observed that encapsulation process enhanced the aqueous dispersibility of genistein and cumulative release of genistein was pH-dependent. More important, after encapsulation data showed that Gen potentiated its antioxidant and antiproliferative effects on HT29 human colon cancer cells by the modulation of endogenous antioxidant enzymes and H2O2 production, which simultaneously activated two different processes of cell death (apoptosis and autophagy), unlike free genistein that only activated one (apoptosis) in a lower proportion. Overall, our data support that Gen-PEG-SiHNM could be potentially used as alternative treatment for colorectal cancer in a near future.

Signals from the caudal diencephalon are required for the projection of the Interstitial Nuclei of Cajal.

Axonal projection is controlled by discrete regions localized at the neuroepithelium, guiding the neurite growth during embryonic development. These regions exert their effect through the expression of a family of chemotropic molecules, which actively participate in the formation of neuronal connections of the central nervous system in vertebrates. Previous studies describe prosomere 1 (P1) as a possible organizer of axonal growth of the rostral rhombencephalon, contributing to the caudal projection of reticulospinal rhombencephalic neurons. This work studies the contribution of chemotropic signals from P1 or pretectal medial longitudinal fascicle (MLF) neurons upon the caudal projection of the interstitial nuclei of Cajal (INC). By using in ovo surgeries, retrograde axonal labeling, and immunohistochemical techniques, we were able to determine that the absence of P1 generates a failure in the INC caudal projection, while drastically diminishing the reticulospinal rhombencephalic neurons projections. The lack of INC projection significantly decreases the number of reticulospinal neurons projecting to the MLF. We found a 48.6% decrease in the projections to the MLF from the rostral and bulbar areas. Similarly, the observed decrease at prosomere 2 was 51.5%, with 61.8% and 32.4% for prosomeres 3 and 4, respectively; thus, constituting the most affected rostral regions. These results suggest the following possibilities: i, that the axons of the reticulospinal neurons employ the INC projection as a scaffold, fasciculating with this pioneer projection; and ii, that the P1 region, including pretectal MLF neurons, exerts a chemotropic effect upon the INC caudal projection. Nonetheless the identification of these chemotropic signals is still a pending task.

Quercetin conjugated silica particles as novel biofunctional hybrid materials for biological applications.

The aim of this work is to formulate biofunctional hybrid materials (HMs) with quercetin (QC) and silica particles (SiPs) by simple methods such as sol-gel and QC conjugation. Physicochemical characterization included particle size, zeta potential (ζ), FTIR and SEM imaging. Spherical particles with ca. 115 nm in diameter were produced, ζ and FTIR demonstrated that QC conjugation was successfully achieved. Electrochemical analyses performed by cyclic voltammetry (CV) suggested that potential binding sites between QC and SiPs may be at functional groups from A ring or C ring, affecting the transfer electron of resorcinol moiety. Iron chelating activity and lipid peroxidation assays showed that after conjugation to SiPs, QC decreased its metal chelating activity, but anti-radical properties is maintained. Our results demonstrated that our proposed method is simple and effective to obtain bio-functional HMs. Our findings prove to be useful in the design of protective approaches against lipid oxidation in food, pharmaceutical, and cosmetics fields.

Common Beans and Their Non-Digestible Fraction: Cancer Inhibitory Activity-An Overview.

The US Department of Agriculture's MyPyramid guidelines introduced a near doubling of the dietary recommendations for vegetables including dry beans-an important food staple in many traditional diets that can improve public health and nutrition. Populations with high legume (peas, beans, lentils) consumption have a low risk of cancer and chronic degenerative diseases. Common beans (Phaseolus vulgaris L.) are known as a rich, reliable source of non-digested compounds like fiber, phenolics, peptides and phytochemicals that are associated with health benefits. Emerging evidence indicates that common bean consumption is associated with reduced cancer risk in human populations, inhibiting carcinogenesis in animal models and inducing cell cycle arrest and apoptosis in cell cultures. Fiber may reduce the risk of premature death from all causes, whereas the whole non-digestible fraction from common beans exhibits anti-proliferative activity and induces apoptosis in vitro and in vivo colon cancer. The mechanisms responsible for this apparently protective role may include gene-nutrient interactions and modulation of proteins' expression. This review investigates the potential health benefits and bioactivity of beans on tumor inhibition, highlighting studies involving functional compounds, mainly non-digestible fractions that modulate genes and proteins, thereby, unraveling their preventive role against the development of cancer.

Vitamin B-12 supplementation of rural Mexican women changes biochemical vitamin B-12 status indicators but does not affect hematology or a bone turnover marker.

A high prevalence of low serum vitamin B-12 concentrations has been reported in studies and surveys in Latin America including Mexico, but the functional consequences are unknown. This randomized controlled trial assessed the response to a high-dose vitamin B-12 supplementation of women in rural Querétaro, Mexico. Participants aged 20-59 y were stratified at baseline to deficient, marginal, and adequate status groups (serum vitamin B-12, 75-148, 149-220, and >220 pmol/L, respectively), and each group was randomized to vitamin B-12 treatment (single dose of 1 mg i.m. then 500 µg/d orally for 3 mo, n = 70) or placebo (n = 62). Measures at baseline and 3 mo included: complete blood count, serum vitamin B-12, holotranscobalamin (holoTC), folate, ferritin, C-reactive protein (CRP), bone alkaline phosphatase, and methylmalonic acid (MMA) and plasma total homocysteine (tHcy). At baseline, 11% of the women were vitamin B-12 deficient and 22% had marginal status. HoloTC was low (<35 pmol/L) in 23% and correlated with serum vitamin B-12 (r = 0.7; P < 0.001). Elevated MMA (>271 nmol/L) and tHcy (>12 µmol/L) occurred in 21 and 31%, respectively, and correlated with serum vitamin B-12 (r = -0.28, P < 0.0007 and r = -0.20, P < 0.01, respectively). Supplementation increased serum vitamin B-12 and holoTC and lowered MMA and tHcy, normalizing all values except for elevated tHcy in 21% of the women. Supplementation did not affect hematology or bone-specific alkaline phosphatase. Vitamin B-12 supplementation normalized biochemical indicators of vitamin B-12 status in the treatment group but did not affect the functional outcomes measured.

Non-digestible fraction of cooked bean (Phaseolus vulgaris L.) cultivar Bayo Madero suppresses colonic aberrant crypt foci in azoxymethane-induced rats.

The non-digestible fraction (NDF) of common bean (Phaseolus vulgaris L.) cultivar Bayo Madero was evaluated for its chemopreventive effect on azoxymethane (AOM) induced aberrant crypt foci (ACF) in rats. Diets containing cooked beans (CB) or its non-digestible fraction (NDF) were fed to 72 male rats after 2 azoxymethane injections (15 mg kg(-1) of body weight once a week for 2 weeks). ACF number, short chain fatty acids (SCFA) and ß-glucuronidase activity were measured in colon sections from rats sacrificed 7 weeks after the last AOM injection. Food intake and weight gain of rats were unaffected by CB and NDF. CB and NDF suppressed the AOM-induced formation of ACF (0.8 and 1.5 ACF/distal zone, respectively vs. 6.6 ACF/distal zone based on methylene blue stain) and lowered ß-glucuronidase activity in cecal, colonic and fecal content compared to AOM group. SCFA production was not significantly different among fecal, cecal and colonic content. These results indicate that CB and NDF from Bayo Madero provide direct chemoprotection against early stage of azoxymethane (AOM)-induced colon cancer in rats.